Bénédicte Delcoigne1, Ali Manouchehrinia2, Christian Barro2, Pascal Benkert2, Zuzanna Michalak2, Ludwig Kappos2, David Leppert2, Jon A Tsai2, Tatiana Plavina2, Bernd C Kieseier2, Jan Lycke2, Lars Alfredsson2, Ingrid Kockum2, Jens Kuhle2, Tomas Olsson2, Fredrik Piehl2. 1. From the Department of Medicine Solna, Clinical Epidemiology Division (B.D.), The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience (A.M., I.K., T.O., F.P.), and Institute of Environmental Medicine (L.A.), Karolinska Institutet; Centre for Molecular Medicine (A.M., I.K., T.O., F.P.), Karolinska University Hospital, Stockholm, Sweden; Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research (C.B., Z.M., L.K., D.L., J.K.), and Clinical Trial Unit, Department of Clinical Research (P.B.), University Hospital Basel, University of Basel, Switzerland; Sanofi Genzyme (J.A.T.), Stockholm, Sweden; Biogen (T.P., B.C.K.), Cambridge, MA; Department of Neurology, Medical Faculty (B.C.K.), Heinrich-Heine University, Duesseldorf, Germany; and Institution of Neuroscience and Physiology (J.L.), Sahlgrenska Academy, University of Gothenburg, Sweden. benedicte.delcoigne@ki.se. 2. From the Department of Medicine Solna, Clinical Epidemiology Division (B.D.), The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience (A.M., I.K., T.O., F.P.), and Institute of Environmental Medicine (L.A.), Karolinska Institutet; Centre for Molecular Medicine (A.M., I.K., T.O., F.P.), Karolinska University Hospital, Stockholm, Sweden; Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research (C.B., Z.M., L.K., D.L., J.K.), and Clinical Trial Unit, Department of Clinical Research (P.B.), University Hospital Basel, University of Basel, Switzerland; Sanofi Genzyme (J.A.T.), Stockholm, Sweden; Biogen (T.P., B.C.K.), Cambridge, MA; Department of Neurology, Medical Faculty (B.C.K.), Heinrich-Heine University, Duesseldorf, Germany; and Institution of Neuroscience and Physiology (J.L.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Abstract
OBJECTIVE: To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS). METHODS: Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide). RESULTS: The baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations. CONCLUSION: Choice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.
OBJECTIVE: To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS). METHODS: Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide). RESULTS: The baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations. CONCLUSION: Choice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.
Authors: Nicole Rübsamen; Eline A J Willemse; David Leppert; Heinz Wiendl; Matthias Nauck; André Karch; Jens Kuhle; Klaus Berger Journal: Front Neurol Date: 2022-06-14 Impact factor: 4.086
Authors: Adriel S Moraes; Vinicius O Boldrini; Alliny C Dionete; Marilia D Andrade; Ana Leda F Longhini; Irene Santos; Amanda D R Lima; Veronica A P G Silva; Rafael P C Dias Carneiro; Raphael P S Quintiliano; Breno B Ferrari; Alfredo Damasceno; Fernando Pradella; Alessandro S Farias; Charles P Tilbery; Renan B Domingues; Carlos Senne; Gustavo B P Fernandes; Felipe von Glehn; Carlos Otavio Brandão; Carla R A V Stella; Leonilda M B Santos Journal: Front Cell Neurosci Date: 2021-07-26 Impact factor: 5.505
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Authors: Lauren G Friedman; Nicholas McKeehan; Yuko Hara; Jeffrey L Cummings; Dawn C Matthews; Jian Zhu; Richard C Mohs; Deli Wang; Suzanne B Hendrix; Melanie Quintana; Lon S Schneider; Michael Grundman; Samuel P Dickson; Howard H Feldman; Judith Jaeger; Elizabeth C Finger; J Michael Ryan; Debra Niehoff; Susan L-J Dickinson; Jessica T Markowitz; Meriel Owen; Alessio Travaglia; Howard M Fillit Journal: Neurology Date: 2021-03-05 Impact factor: 9.910